M-(amino-s-triazolyl)benzene-sulfonamides and their production

ABSTRACT

Amino-s-triazolybenzenesulfonamides having the formula WHERE EACH OF R1 and R2 is hydrogen or methyl, and X is hydrogen, methyl, methoxy, or halogen, and salts thereof are produced by cyclizing a sulfamoylbenzoic acid 2-amidinohydrazide. The compounds of the invention are useful as pharmacological agents having antiviral activity.

United States Patent Hoefle et al.

[4 1 May 30, 1972 [54] M-(AMINO-S-TRIAZOLYUBENZENE- SULFONAMIDES ANDTHEIR PRODUCTION [72] Inventors: Milton L. Hoefle; Ann Holmes, both ofAnn Arbor, Mich.

[73] Assignee: Parke, David & Company, Detroit, Mich.

[22] Filed: July 6, 1970 [21] Appl. No.2 52,720

[52] U.S. Cl ..260/308 R, 260/465 D, 260/470, 260/515 A, 260/518 R,260/518 A, 260/556 AR,

[51] Int. Cl. ..C07d 55/06 [58] Field of Search ..260/308 R [56]References Cited UNITED STATES PATENTS 2,989,539 6/1961 Anderson et a1..260/310 Primary Examiner-Alton D. Rollins Attorney-Robert R. Adams,David B. Ehrlinger, George M. Richards and Edward J. Gall 571 ABSTRACTAmino-s-triazolylbenzenesulfonamides having the formula QRPZOL NmRr-HNOgS where each of R. and R is hydrogen or methyl, and X ishypharmacological agents having antiviral activity.

10 Claims, No Drawings M-(AMlNO-S-TRIAZOLYUBENZENE-SULFONAMIDFS ANDTHEIR PRODUCTION SUMMARY AND DETAILED DESCRIPTION and topharmaceutically acceptable salts thereof; where each of R, and R ishydrogen or methyl, and X represents hydrogen, methyl, methoxy, andhalogen. Preferred halogens represented by X are chlorine and bromine.

ln accordance with the invention, compounds having the foregoing formulaand salts thereof are produced by the cyclization of a sulfamoylbenzoicacid 2-amidinohydrazide compound having the formula where each of R,, Rand X has the aforementioned significance. The cyclization is bestaccomplished by heating the compound of formula ll, in free base form,or preferably, in salt form, in solution in the presence of a base. Thetemperature and duration are not especially critical and may be varied.It is most convenient to heat the solution containing the chosenstarting material and base to the boiling point, and at thattemperature, the cyclization is essentially complete after a period ofabout 5 to 60 minutes. Any of a number of bases may be used to catalyzethe cyclization, including alkali metal hydroxides, alkali metalcarbonates, alkaline earth metal hydroxides, alkaline earth metalcarbonates, ammonia, and tertiary amines, such as pyridine, quinoline,triethylamine, and N,N-dimethylaniline. The preferred bases are analkali metal hydroxide, especially sodium hydroxide, and ammonia. Thepreferred solvent for use with the foregoing bases is water, although anumber of water-miscible solvents, including lower alkanols, dioxane,tetrahydrofuran, and dimethylsulfoxide, can also be used, either aloneor mixed with water. When the starting sulfamoylbenzoic acidZ-amidinohydrazide compound is used in salt fonn, at least enough baseis used to neutralize the salt. The amount of base over and above thatrequired for neutralization of the salt form is not critical. Theamino-striazolylbenzenesulfonamide product of the reaction can beisolated in the free form having formula 1 above or in salt form byappropriate adjustment of the pH of the reaction mixture.

The cyclization of the compound of formula ll can also be accomplishedsimply by heating it, in free base form, in solution at an elevatedtemperature in the absence of any added base. Added base is not strictlyrequired in such a case because the sulfamoylbenzoic acid 2-amidinohydrizide starting material in free base form is sufficientlybasic to permit the intramolecular cyclization reaction to proceed tocompletion. In effecting the cyclization in this way, the same solventsand reaction conditions as those given above may be used, and inaddition, the aromatic hydrocarbons benzene and toluene may also be usedas solvent. lf benzene and toluene are used, the course of thecyclization can be determined by heating the reaction mixture to boilingand collecting and measuring the water that is given off as a by-productof the reaction.

2 The sulfarnoylbenzoic acid 2 -amidinohydrazide compounds of formula lland salts thereof that are used as starting materials in the foregoingprocess are prepared by reacting a sulfamoylb'enzoi'c acid hydrazidecompound having the formuwith anacid -addition salt of a reactiveguanidine compound, which is preferably3,5-dimethylpyrazole-l-carboxamidine nitrate. While the sulfamoylbenzoicacid 2-amidinohydrazide starting material can be isolated, preferably insalt form, prior to cyclization, it is more convenient and preferable toprepare this starting material in situ, in nitrate salt form, when 3,5-dimethylpyrazole-l-carboxamidine nitrate is used in the reaction withthe hydrazide of formula III, and then react it further with base in thecyclization process described above without isolation.

The sulfamoylbenzoic acid hydrazide intermediates of formula lll aboveare prepared by the following general method. A benzoic acid compoundhaving the formula is reacted with chlorosulfonic acid to give achlorosulfonylbenzoic acid compound having the formula C O OH ClOrSwhich is next reacted with ammonia or methylamine, and the is in turnreacted either with methanol in the presence of hydrogen chloride togive a sulfamoylbenzoic acid, methyl ester, having the formula,

-OCH:

Rl-HN 0 S VII or with chloroacetonitrile in the presence oftriethylamine to give a sulfamoylbenzoic acid, cyanomethyl ester, havingthe formula, l- 1 2 lh-IINOgS VIII and either of the two intermediateesters is finally reacted with hydrazine or with monomethyl hydrazine togive the desired sulfamoylbenzoic acid hydrazide intermediate havingformula III. In formulas IV, V, VI, VII, and VIII, each of R and)( hasthe same meaning as previously given.

The compounds of the invention can exist in the free form having formulaI above or in salt form. Pharmaceutically acceptable acid-addition saltsare formed as described above or by reaction of the freeamino-s-triazolylbenzenesulfonamide compounds with any of a number ofinorganic and organic acids, including hydrochloroic, hydrobromic,hydriodic, nitric, sulfuric, phosphoric, acetic, benzoic, salicylic,methane-sulfonic, benzenesulfonic, succinic, maleic, tartaric, andcitric acids. Pharmaceutically-acceptable salts are also formed byreacting the free amino-s-triazolylbenzenesulfonamides with a strongbase. Suitable strong bases for this purpose include alkali metalhydroxides, such as sodium hydroxide, potassium hydroxide, and lithiumhydroxide; alkali metal hydrides, such as sodium hydride; alkali metalalkoxides; and alkaline earth metal hydroxides. The freeamino-s-triazolylbenzenesulfonamide compounds and their salts may differsomewhat in certain physical properties, such as solubility in polarsolvents, but they are otherwise equivalent for purposes of theinvention.

The compounds of the invention can also exist in anhydrous form as wellas in solvated, including hydrated, forms.' In general, the hydratedforms and the solvated forms with pharmaceutically-acceptable solventsare equivalent to the anhydrous or unsolvated form for the purposes ofthe invention.

The compounds of the invention are new chemical compounds that areuseful as pharmacological agents, especially as antiviral agents. Assuch, they have been found to be active against a number of differentviruses, including Coxsackie and polio viruses, as well as variousstrains of rhinovirus.

The antiviral activity of the compounds of the invention can bedemonstrated in and quantitatively measured by a test that utilizes themethod of Rightsel, et a]. (J. Immunol., Vol. 76, pages 464-474 I956);Univ. Mich. Med. BulL, Vol. 24, pages 222-234 1958)] and is carried outin vinyl plastic panels with a monolayer of H. Ep. No. 2 cells. In thistest, the effect of a test compound on the host cell and on thecytopathic effect (CPE) of the virus, which is present at a level thatis 32 times the 50 percent tissue culture infective dose (32 TClD isevaluated microscopically and expressed numerically by what is termedthe virus rating (VR). The VR is a measure of the inhibition of thevirus CPE by the test compound at levels that are nontoxic or partiallytoxic for the host cells. The calculation of the VR for a given testcompound is carried out as follows. (See also Ehrlich et. al., Ann N.Y.Acad. Sci., Vol. 130, pages 5-16, especially page 7, 1965.)

Each test compound is normally evaluated in triplicate panels at fivelevels: undiluted and at dilutions of 3.2-fold, fold, 32-fold, andlOO-fold. The value assigned to the CPE of the treated infected cells ateach test level is subtracted from that of the untreated but infectedcontrols, and the differences (C-T) for all levels are summed up. If thetest compound is partially toxic for the host cell at any test level,the difference (C-T) for that level is halved before being included inthe summation. The VR is then finally arrived at by dividing thesummation by 10. A VR of 1.0 or greater is considered an indication ofantiviral activity.

The virus ratings obtained for some representative compounds of thepresent invention when tested by the method described above againstCoxsackie, polio, and rhinovirus 1A viruses are presented in thefollowing table.

The invention is illustrated by the following examples. Example 1 Amixture of 21.7 g. of 3-(methylsulfamoyl)benzoic acid hydrazide, 20 g.of 3,5-dimethylpyrazole-l-carboxamidine nitrate, and 100 ml. of water isheated under reflux for 18 hours and then allowed to cool to roomtemperature. To the reaction mixture, which contains the nitrate salt of3-( methylsulfarnoyl)benzoic acid 2-amidinohydrazide, is added 5 ml. of50 percent aqueous sodium hydroxide, and the resulting mixture is heatedto the boiling point and cooled. The cooled alkaline mixture isneutralized with glacial acetic acid, and upon standing, there isobtained a solid precipitate of m-(5-aminostriazol-3-yl)-N-methylbenzenesulfonamide, which is isolated andpurified by crystallization from water; m.p. 202-203 C.

The 3-( methylsulfamoyl)benzoic acid hydrazide starting material isobtained as follows. To 1.3 liters of chlorosulfonic acid, stirred atroom temperature, is added in portions 244.3 g. of benzoic acid, and theresulting mixture is heated at l20-l25C. until hydrogen chlorideevolution ceases. The mixture is then cooled and treated with excess icewater, and the colorless solid 3-chlorosulfonylbenzoic acid thatprecipitates is isolated and used in the next step without furtherpurification. To l liter of 40 percent aqueous methylamine, stirred at 0C., is carefully added 440 g. of 3- chlorosulfonylbenzoic acid, and theresulting mixture is kept at room temperature overnight. It is thenacidified with hydrochloric acid, and upon cooling, there is obtained asolid precipitate of 3-(methylsulfamoyl )benzoic acid, which isisolated, washed with cold water, and dried under reduced pressure; m.p.205208C. Into a mixture of 408.8 g. of 3- rnethylsulfamoynbenzoic acidand 2 liters of methanol at room, temperature is bubbled anhydroushydrogen chloride for one hour. The resulting clear solution is thenheated under reflux for one hour more and evaporated to dryness underreduced pressure to give a solid residue of 3-( methylsulfamoyl)benzoicacid, methyl ester, which is isolated and used in the next reaction stepwithout further purification. To a stirred mixture of 435.1 g. of 3-(methylsulfamoyl)-benzoic acid, methyl ester and 2 liters of methanol isadded 600 ml. of percent hydrazine hydrate, and the resulting mixture isheated under reflux for about 18 hours and then evaporated under reducedpressure. The residue is treated with water, and the aqueous mixture isneutralized with hydrochloric acid to give, upon cooling, a solidprecipitate of 3-(methylsulfamoyl)benzoic acid hydrazide; m.p. l35-l38C., following crystallization from water and drying under reducedpressure. Example 2 A mixture consisting of 39.1 g. of4-chloro-3-sulfamoylbenzoic acid hydrazide, 31.5 g. of3,5-dimethylpyrazole-l-carboxamidine nitrate, and 50 ml. of water isheated under reflux for 5 hours, cooled to room temperature, and madealkaline (pH approximately 9) with ammonium hydroxide. The resultingalkaline mixture is chilled, and the solid 4-chloro-3- sulfamoylbenzoicacid Z-amidinohydrazide that precipitates is isolated and crystallizedfrom a mixture of I00 ml. of water and 15 ml. of concentratedhydrochloric acid to give the hydrochloride salt of4-chloro-3-sulfamoylbenzoic acid 2- amidinohydrazide; m.p. 259-26lC.This salt is added to a mixture of 500 ml. of water and ml. of 50percent aqueous sodium hydroxide, and the resulting mixture is heated tothe boiling point, cooled, and neutralized with glacial acetic acid. Theneutralized mixture is then chilled further, and the solid precipitateof 5-( 5-amino-s-triazol-3-yl)-2-chlorobenzene-sulfonamide that isobtained is isolated and purified by crystallization from aqueousethanol; m.p. 285286 C.

A solution of 1.0 g. of 5-( 5-amino-s-triazol-3-yl)-2-chlorobenzenesulfonamide in 75 ml. of ethanol is treated with activatedcharcoal, filtered, and to the filtrate is added 2 ml. of ethyl acetatesaturated with hydrogen chloride. The resulting mixture is concentratedby boiling in an open flask to a volume of ml. During the heating, 1.0ml. more of saturated hydrogen chloride in ethyl acetate solution isadded. Upon cooling, there is obtained a solid precipitate ofS-(S-amino-striazol-3-yl)-2-chlorobenzene-sulfonamide hydrochloride;m.p. 289-29 1 C.

Example 3 A mixture consisting of 27.5 g. of4-chloro-3-(methylsulfamoyl)benzoic acid l-methylhydrazide, g. of 3,5-dimethylpyrazole-l-carboxamidine nitrate, and 100 ml. of water is heatedunder reflux for 18 hours and then cooled to room temperature. To thereaction mixture, which contains the nitrate salt of4-chloro-3-(methylsulfamoyl)-benzoic acid 2-amidino-l-methylhydrazide,is added 5 ml. of 50 percent aqueous sodium hydroxide, and the resultingmixture is heated to the boiling point, cooled, and neutralized withglacial acetic acid. Upon standing,5-(3-amino-1-methyl-s-triazol-5-yl)-2- chloro-N-methylbenzenesulfonamideseparates from the neutral mixture as an oil, which is isolated andpurified by crystallization from ethanol; m.p. l96-197 C.

The 4-chloro-3-(methylsulfamoyhbenzoic acid l-methylhydrazide isprepared as follows. A solution of 10.0 g. of 4-chloro-3-(methylsulfamoyl)benzoic acid cyanomethyl ester in 50 ml. ofmonomethylhydrazine is kept at room temperature for 6 hours and dilutedwith an equal volume of percent aqueous acetic acid, and the solid4-chloro-3-(methylsulfamoyl)-benzoic acid l-methylhydrazide thatprecipitates is isolated and dried. It is suitable for use withoutfurther purification.

Example 4 A mixture consisting of 36.1 g. of 4-bromo-3-sulfamoylbenzoicacid hydrazide, 25 g. of 3,5-dimethylpyrazole-l-carboxamidine nitrate,and 200 ml. of water is heated under reflux for 18 hours and then cooledto room temperature. The reaction mixture, which contains the nitratesalt of 4-bromo-3- sulfamoylbenzoic acid 2-amidinohydrazide, is madealkaline with ammonium hydroxide, and the alkaline mixture is brieflyheated at the boiling point, cooled, and neutralized with glacial aceticacid. Upon further cooling, there is obtained from the neutral mixture asolid precipitate of S-(S-amino-s-triazol-3-yl)-2-bromobenzenesulfonamide, which is isolated and purified bycrystallization from water; mp. 29 -296C.

A solution of 3.2 g. of 5-(5-amino-striazol-3-yl)-2-bromobenzenesulfonamide in 75 ml. of methanol is treated with activatedcharcoal, filtered, and to the filtrate is added a solution of 1.1 g. ofsodium methoxide in 25 ml. of methanol. After minutes at roomtemperature, the mixture is concentrated to half-volume, cooled, andslowly poured with stirring into ether to give a colorless solidprecipitate of S-(S-amino-striazol-3-yl)-2-bromobenzenesulfonamide,monosodium salt, which is isolated and dried.

Example 5 A mixture consisting of 30.8 g. of4-bromo-3-(methylsulfamoyl)benzoic acid hydrazide, 20 g. of3,5-dimethylpyrazole-l-carboxamidine nitrate, and 100 ml. of water isheated under reflux for 18 hours and then cooled to room temperature. Tothe reaction mixture, which contains the nitrate salt of4-bromo-3-(methylsulfamoyl)benzoic acid 2- amidinohydrazide, is added 5ml. of 50 percent aqueous sodium hydroxide, and the resulting mixture isbriefly heated at the boiling point, cooled, and neutralized withglacial acetic acid. The oily residue that separates is isolated andtriturated '6 with ethanol to'give solid 5-(5-arnino-s-triazol-3-yl)-2-bromo- N-methylbenzenesulfonamide; m.p.240242 C., following crystallization from ethanol.

The 4-bromo-3-(methylsulfamoyl)benzoic acid hydrazide starting materialis obtained as follows. Anhydrous hydrogen chloride is bubbled into amixture of 73.4 g. of 4-bromo-5- (methylsulfamoyl)benzoic acid and 300ml. of methanol at room temperature for 30 minutes, and the resultingmixture is heated under reflux for 30 minutes more. The reaction mixtureis then evaporated to dryness under reduced pressure to give a solidresidue of 4-bromo-3-(methylsulfamoyl)benzoic acid, methyl ester; m.p.170 C. A mixture consisting of 77 g. of this ester intermediate, 70 ml.of percent hydrazine hydrate, and 200 ml. of methanol is heated underreflux for 2 hours and is then evaporated to dryness under reducedpressure to give a solid residue of 4-bromo-3-(methylsulfamoyl)benzoicacid hydrazide, which is washed with cold water and purified bycrystallization from water; m.p. 98-l00 C Example 6:

A mixture consisting of 30.8 g. of 2-bromo-5-(methylsulfamoyl)benzoicacid hydrazide, 20 g. of 3,5-dimethylpyrazole-l-carboxamidine nitrate,and 100 ml. of water is heated under reflux for 18 hours and then cooledto room temperature. The viscous oil that separates, which is thenitrate salt of 2-bromo-5-(methylsulfamoyl)benzoic acid 2-amidinohydrazide, is isolated by decantation and mixed with 15 m]. of 50percent aqueous sodium hydroxide and 100 ml. of water, and the resultingmixture is heated under reflux for 5 minutes. Upon cooling, it istreated with sufficient acetic acid to render it just slightly alkaline,and the gummy precipitate of3-(5-arnino-s-triazol-3-yl)-4-bromo-N-methylbenzenesulfonamide that isobtained is isolated and purified by crystallization from 50 percentaqueous ethanol; m.p. 237-238 C.

The 2-bromo-5-(methylsulfamoyl)benzoic acid hydrazide starting materialis obtained as follows. Anhydrous hydrogen chloride is bubbled into amixture of 147 g. of 2-bromo-5- (methylsulfamoyl)benzoic acid and 500ml. of methanol at room temperature for 30 minutes, and the resultingmixture is heated under reflux for 30 minutes more. The reaction mixtureis then evaporated to dryness under reduced pressure to give a solidresidue of 2-bromo-5-(methylsulfamoyl)benzoic acid, methyl ester, whichis suitable for use without further purification. To a stirred mixtureof 154 g. of this ester intermediate and 500 ml. of methanol is addedml. of 85 percent hydrazine hydrate, and the resulting mixture is heatedunder reflux for 3.5 hours, cooled, and evaporated under reducedpressure. Theresidue is mixed with water, and the aqueous mixture ischilled to give solid 2-bromo-5-(methylsulfamoyl-benzoic acid hydrazide;m.p. l75-l76C., following crystallization from water and drying underreduced pressure.

Example 7 A mixture consisting of 23.8 g. of4-methyl-3-(methylsulfamoyl)benzoic acid hydrazide, 20 g. of3,5-dimethylpyrazole-l-carboxamidine nitrate, and 100 ml. of water isheated under reflux for 18 hours, filtered while hot to remove insolublematerial, and then cooled to room temperature. To the reaction mixture,which contains the nitrate salt of 4- methyl-3-( methylsulfamoyl)benzoicacid Z-amidinohydrazide, is added 16 g. of sodium hydroxide, and theresulting strongly alkaline solution is heated under reflux for 5minutes. It is then treated with activated charcoal and filtered, and tothe filtrate is added 7 ml. of acetic acid. Upon standing, there isobtained from the acidified filtrate a solid precipitate of 5-(S-amino-striazol-3-yl)-N-methyl-o-toluene-sulfonamide, which is isolatedand purified by crystallization from aqueous ethanol; m.p. 228-229 C.

The 4-methy1-3-(methylsulfamoyl)benzoic acid hydrazide starting materialis obtained as follows. Anhydrous hydrogen chloride is bubbled into amixture of 86.0 g. of 3-(methylsulfamoyl)-p-toluic acid and 300 ml. ofmethanol at room temperature for 30 minutes, and the resulting mixtureis heated under reflux for 30 minutes more. The reaction mixture is thenevaporated to dryness under reduced pressure to give a residue of3-(methylsulfamoyl)-p-toluic acid, methyl ester; m.p. l25l27 C.,following trituration with cold water. To a stirred mixture of 86.6 g.of this ester intermediate and 300 ml. of methanol at room temperatureis added 75 ml. of 85 percent hydrazine hydrate, and the resultingmixture is heated under reflux for about 18 hours. It is then evaporatedunder reduced pressure, and the residue is dissolved in water, Theaqueous solution is treated with activated charcoal and filtered, andthe filtrate is acidified with hydrochloric acid to about pH 4. Uponcooling, there is obtained from the acidic filtrate a solid precipitateof 3-( methylsulfamoyl)-p-toluic acid hydrazide; m.p. l35-137 C.

Example 8 A mixture consisting of 25.9 g. of4-methoxy-3-(methylsulfamoyl)benzoic acid hydrazide, 20 g. of3,5-dimethylpyrazolel-carboxamidine nitrate, and 100 ml. of water isheated under reflux for 18 hours and then cooled to room temperature. Tothe reaction mixture, which contains the nitrate salt of4-methoxy-3-(methylsulfamoyl)benzoiic acid 2- amidinohydrazide, is added10 ml. of 50 percent aqueous sodium hydroxide, and the resulting mixtureis briefly heated at the boiling point, cooled, and neutralized withglacial acetic acid. Upon standing, there is obtained from theneutralized mixture a solid precipitate of 3-(5-amino-s-triazol-3-yD-6-methoxy-N-methylbenzenesulfonamide; m.p. 230232 C., followingcrystallization from water.

The 4-methoxy-3-(methylsulfamoyl)benzoic acid hydrazide startingmaterial is obtained as follows. Anhydrous hydrogen chloride is bubbledinto a mixture of 73.5 g. of 4-methoxy-3- (methylsulfamoyl)benzoic acidand 300 ml. of methanol at room temperature for 30 minutes, and theresulting mixture is heated under reflux for 30 minutes more. Thereaction mixture is then evaporated to dryness under reduced pressure togive a solid residue of 4-methoxy-3-(methylsulfamoyl )benzoic acid,methyl ester; m.p. l25l27C. To a mixture of 77.7 g. of this esterintermediate and 300 ml. of methanol is added 120 ml. of 85 percenthydrazine hydrate, and the resulting mixture is heated under reflux for12 hours, cooled, and evaporated under reduced pressure. To the residueis added a small amount of cold water, and the aqueous mixture isfiltered to give 4-methoxy-3-(methylsulfamoyl)benzoic acid hydrazide,which is dried under reduced pressure and purified by crystallizationfrom water; m.p. l75l 76C.

We claim:

I. A member of the class consisting ofamino-s-triazolylbenzenesulfonamide compounds having the formula andphannaceutically-acceptable salts thereof; where each of R and R ishydrogen or methyl, and X represents a member of the class consisting ofhydrogen, methyl, methoxy, and halogen.

2. A compound according to claim 1 which is m-( 5-amino-striazol-3-yl(-N-methylbenzenesulfonarnide.

3. A compound according to claim 1 which is 5-( S-amino-striazol-3-yl)-2-chlorobenzenesulfonamide.

4. A compound according to claim 1 which is 5-(3-amino-lmethyl-s-triazol-S-yl )-2-chloro-N-met.hylbenze ne-sulfonamide.

5. A compound according to claim 1 which is 5-( S-amino-striazol-3-yl)-2-bromobenzenesulfonamide.

6. A compound according to claim 1 which isS-(S-amino-striazol-3-yl)-2-bromo-N-methylbenzenesulfonamide.

7. A compound according to claim 1 which is 3-(S-amino-striazol-3-yl)-4-bromo-N-methylbenzenesulfonamide.

8. Process for the production of a member of the class consisting ofamino-s-triazolylbenzenesulfonamide compounds having the formula TNTNHQand salts thereof, which comprises cyclizing a member of the classconsisting of sulfamoylbenzoic acid 2-amidino-hydrazide compounds havingthe formula and acid-addition salts thereof; where each of R R and X isdefined as in claim 1.

9. Process according to claim 8 wherein the cyclization is accomplishedby heating the sulfamoylbenzoic acid 2- amidinohydrazide, inacid-addition salt form, with a base.

10. Process according to claim 8 wherein the cyclization is accomplishedby heating the sulfamoylbenzoic acid 2- amidinohydrazide, inacid-addition salt form, with an aqueous alkali metal hydroxide.

2. A compound according to claim 1 which ism-(5-amino-s-triazol-3-yl(-N-methylbenzenesulfonamide.
 3. A compoundaccording to claim 1 which is5-(5-amino-s-triazol-3-yl)-2-chlorobenzenesulfonamide.
 4. A compoundaccording to claim 1 which is5-(3-amino-1-methyl-s-triazol-5-yl)-2-chloro-N-methylbenzene-sulfonamide.5. A compound according to claim 1 which is5-(5-amino-s-triazol-3-yl)-2-bromobenzenesulfonAmide.
 6. A compoundaccording to claim 1 which is5-(5-amino-s-triazol-3-yl)-2-bromo-N-methylbenzenesulfonamide.
 7. Acompound according to claim 1 which is3-(5-amino-s-triazol-3-yl)-4-bromo-N-methylbenzenesulfonamide. 8.Process for the production of a member of the class consisting ofamino-s-triazolylbenzenesulfonamide compounds having the formula andsalts thereof, which comprises cyclizing a member of the classconsisting of sulfamoylbenzoic acid 2-amidino-hydrazide compounds havingthe formula and acid-addition salts thereof; where each of R1, R2, and Xis defined as in claim
 1. 9. Process according to claim 8 wherein thecyclization is accomplished by heating the sulfamoylbenzoic acid2-amidinohydrazide, in acid-addition salt form, with a base.
 10. Processaccording to claim 8 wherein the cyclization is accomplished by heatingthe sulfamoylbenzoic acid 2-amidinohydrazide, in acid-addition saltform, with an aqueous alkali metal hydroxide.